Low-Dose Naltrexone and Gabapentin Interaction: What Patients and Clinicians Need to Know

Is there a known interaction between low-dose naltrexone and gabapentin?

We found no published study that has tested the two together. The naltrexone tablet label says: 'Studies to evaluate possible interactions between naltrexone hydrochloride and drugs other than opiates have not been performed,' and advises caution when naltrexone is given with any other drug [1].

LDN means naltrexone at 0.5 to 6 mg a day, most often 4.5 mg [5], far below the 50 mg tablet FDA approved for alcohol dependence and opioid blockade [1]. No LDN product or LDN indication is FDA-approved; LDN is made by compounding pharmacies, and FDA says it does not verify the safety, effectiveness or quality of compounded drugs before they are marketed [4][5]. A 2026 narrative review of 105 studies, 15 of them randomized trials, concluded that current evidence does not support routine clinical use of LDN [5].

Gabapentin's labeled uses are postherpetic neuralgia in adults and add-on treatment of partial-onset seizures from age 3 up; neuropathic pain from diabetes, anxiety, sleep problems and alcohol withdrawal are off-label [6]. Gralise and Horizant are separate gabapentin-based products.

Why this is not a liver-enzyme interaction

Gabapentin is not metabolized to any appreciable extent, did not inhibit the major hepatic enzymes in the label's in vitro studies, and leaves the body unchanged through the kidneys, with a half-life of about 5 to 7 hours [2]. Its bioavailability falls as the dose rises, from about 60% at 900 mg a day to about 33% at 3,600 mg a day [2].

Naltrexone is handled differently: significant first-pass metabolism, oral bioavailability of 5% to 40%, a major metabolite (6-beta-naltrexol) with a 13-hour half-life, and 53% to 79% of a dose excreted in urine [1]. The naltrexone labels were written for 50 mg tablets and a 380 mg injection; they give no interaction guidance for the milligram doses used as LDN [1][7].

Sedation and breathing: what gabapentin's warning covers

FDA's 2019 safety communication warns that gabapentin can cause serious breathing difficulties in people with respiratory risk factors: opioid pain medicines and other CNS depressants, lung disease such as COPD, and older age [3]. FDA required new respiratory depression warnings in the gabapentinoid labels and advised prescribers to start at the lowest dose and monitor for sedation and respiratory depression when a gabapentinoid is prescribed with an opioid or another CNS depressant such as a benzodiazepine [3].

The opioid part is the best quantified. In an Ontario nested case-control study of 1,256 opioid-related deaths and 4,619 matched controls, gabapentin had been prescribed in the previous 120 days for 12.3% of the people who died versus 6.8% of controls; the adjusted odds ratio for opioid-related death with co-prescribed gabapentin was 1.49 (95% CI 1.18 to 1.88) [8]. That is observational data in people using opioids, not data about LDN.

What has been reported with LDN looks different. In the naltrexone tablet label's open-label study of about 570 people with alcoholism, somnolence was reported by 2% and dizziness by 4% [1]. LDN trials most often report insomnia, vivid dreams, nausea and dizziness [5], and a four-trial meta-analysis in fibromyalgia (222 patients) found vivid dreams and nausea more often with LDN than placebo, with no significant difference in serious adverse events [9].

Does kidney function change the picture?

For gabapentin, yes. It is cleared unchanged by the kidneys [2], and the Neurontin label sets lower maximum daily doses as creatinine clearance falls, for example 200 to 700 mg a day at a clearance above 15 to 29 mL/min.

For LDN, safety data in liver or kidney impairment are sparse [5]. The Vivitrol label recommends caution in moderate to severe renal impairment [7]; that is a different product from oral LDN, and the naltrexone labels give no guidance at LDN doses [5].

Opioids: the interaction that matters most

The naltrexone label contraindicates use in anyone receiving opioid analgesics, anyone currently dependent on opioids (including those maintained on methadone or buprenorphine), and anyone in acute opioid withdrawal; the contraindication is written with no dose exception [1]. The label recommends a minimum of 7 to 10 opioid-free days for people previously dependent on short-acting opioids, and says people moving from buprenorphine or methadone may be vulnerable to precipitated withdrawal for as long as two weeks [1].

This matters here because gabapentin and opioids are both commonly prescribed for pain, and that combination is the one FDA and the Ontario data flag for breathing risk [3][8].

Symptoms FDA says need immediate medical attention

FDA's 2019 communication lists confusion or disorientation, unusual dizziness or lightheadedness, extreme sleepiness or lethargy, slowed, shallow or difficult breathing, unresponsiveness, and bluish or tinted skin on the lips, fingers or toes as reasons to seek medical attention immediately [3].